hepatitis c infection an update

8/2/2019 Hepatitis C Infection an update

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Hepatitis C virus (HCV)

Hepatitis C virus (HCV) infection is themost common chronic blood borneinfection in the United States;

approximately 3.2 million persons arechronically infected. Although HCV is notefficiently transmitted sexually, persons at

risk for infection through injection drug usemight seek care in STD treatmentfacilities, HIV counselling and testing

facilities.

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What is Hepatitis C Infection

Infection withHepatitis Ccauses

1 Chronichepatitis

2 Cirrhosis3 Hepatocellular

Carcinoma4/22/2012 3


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HCV - Virology

Family Flaviviridae

Genus Hepacivirus

A small ( 50 nm )

virusss RNA virus,

positive senstive

RNA sequence

analysis into at leastsix major genotypes(Clades)

There are 100

subtypes.

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Why Hepatitis C is an importantDisease

WHO estimates 170 million ( 3 % ) worldpopulation is infected with HCV.Highest in Egypt.

Lowest in Sweden.In USA 2.7 to 3.4 million people infected.In USA there is a decline since 1990.Those born between 1940 and 1965 hadhighest incidence reaching a peak betweenthe age of 20 to 35 yearsIn USA 25,000 persons die of cirrhosis andchronic liver disease

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How Hepatitis C is transmitted

Bloodtransfusions

Drug absue Injections

Tattooing

Contamination ofMedicalequipment.

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HCVMother to Child transmission

Vertical transmissionoccurs in 3 -10%

Mother with higher

HCV viral loads or coinfection with HIVtransmit in higherrates.

No risk oftransmission isassociated withbreast feeding.

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Transmission of Infection inSpouses

Sexual transmission ofHCV can occur, withmuch lower frequencythan that of HIV, and HBVLong term partners ofHCV infected patientshave higher rates ofinfection than the generalpopulation.May be associated with

shared use of Razors andtooth brushes.

Dr.T.V.Rao MD

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CDC on Spouse Transmission

CDC on the basisof current evidence

does notrecommend use ofbarrier precautionsamong theheterosexualmonogamouscouples, to prevent

HCV transmission.4/22/2012 12


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Higher incidence of HCVInfections

Increased prevalencein

Sexuallytransmitteddiseases.

HIV co infection.Injecting druguse.

High risk sexualpractices.

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Health care devices and HCV

WHO calculates that unsafehealth care devices accountfor 2.3 million new HCVinfections per year, and200 000 HCV related

premature deaths, mostly inDeveloping countries

The re-use of injectionequipment's withoutsterilization contributes tomajor spread.

WHO estimates that about40% of injection relatedequipment is reused inDevloping countries.

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HCV and Blood Transfusions

Blood transfusionsfrom unscreeneddonors and unsafetherapeuticprocedures are majormodes oftransmission inDeveloping countries.

Paid donors are graverisk

Dr.T.V.Rao MD

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Trends of Change in

Transmission

Education among thedrug abusers, blooddonor screening needleexchange programmes

have remarkablyreduced the incidence.

Sexual, and Perinataltransmission has gained

importance.

Dr.T.V.Rao MD

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Needle Stick Injuries

A CDC report suggestedrisk of HCV transmissionis about six times higherper needle stick exposurethan is the risk with HIVinfection

( 1.8% vs0.35 )

Dr.T.V.Rao MD

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Onset of Infection in HCV

The average incubationperiod for HCV is 6-7days

The period for exposureto seroconversion is 8-9weeks.

About 90% of the infectedare anti HCV positive in 5months

Dr.T.V.Rao MD

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How Virus C replicates inHepatocytes

Depends on cellular factors and

shared by viral proteins.Replicates with viral and host

proteins

Multiplication rate is very high aTrillion particles are producedevery day.

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Pathology of HCV infection

Virus causes inflammation of Liver

Microscopically spotted parenchymal celldegeneration

Necrosis of Hepatocytes

Causes diffuse lobular inflammatory reaction

Disruption of liver cell cords

Accumulation of Macrophages neardegenerating Hepatocytes.

Dr.T.V.Rao MD

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Pathology

Both Hepatitis B and Care cytopathogenicCellular damage is

immune mediatedBoth HBV and HBC havesignificant roles in in thedevelopment ofHepatocellularcarcinomaCarcinoma may appear15 60 years after thebeginning of infection.

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Viral clearance from Hepatocytes

Virus clears either spontaneously or

by treatmentMay lead to cure, even fibrosis isregresses

Normalization of enzymes liverenzymes on clearance of virus

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Clinical course of Hepatitis CInfection

Acute HCV infection is asymptomatic

in most patients.

Natural history and chronicity ratevaries much between the populationgroups.

Persistence of virus has been definedas detectable HCV RNA for morethan 6 months from the time of

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Progress of HCV infections

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How Acute Infection Manifests

Symptomatic infection in only 15 % ofthe infected

Spontaneous clearance is higher inpatients present with symptomaticthan an asymptomatic acute HCVinfections

Major studies suggest that chronicityrates might depend on the mode ofinfection, and the age at which patient

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Acute manifestations

Only 10-20% of allacutely infected patientsdevelop Jaundice, Higher

incidence of Jaundice isin injecting drug users

Fatigue,myalgia,lowgrade fever.

Right upper quadrantpain,nausea or vomiting

Dr.T.V.Rao MD

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Other clinical Manifestations

Influenza likeillness

Dark colored urineClay colored stool

Jaundice is more

indicative ofdisease

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Progress of events in HCVInfection

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Bio Chemical marker

Concentration of Alanineaminotransferase greater than tentimes the upper limit of normal areuncommon.Even few cases symptomatic HCVinfection have reported increase up to20 timesThe presence of jaundice might be anindicator of an effective host immuneresponse, leads to spontaneous viralclearance.4/22/2012 29


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Diagnosis of HCV Infection

No definitive pathological test todiagnose acute HCV infection.

Diagnosis is supported by,

Identifiable exposure to HCV

Recent seroconversion

Marked increased concentration ofliver

enzymes

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Serology in Diagnosis

Detection of antibodies against HCVimmunoassay is unreliable to identify acuteinfectionsAntibodies may be absent in acute stageThe appearance of antibodies against HCVcould be delayed in as many as 30% ofpatients at the onset of symptoms,particularly in Immunosuppressed.IgMantibodies against HCV have not provenuseful in diagnosis of acute HCVinfections, as their concentration remainfairly constant in both acute and chronicinfections.4/22/2012 31


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RNA estimation in HCV

infections

HCV RNA levels couldfluctuate ( may beundetectable ) up to a

year after theinfection,necessitating serialmeasurements ofHCV RNA for a period

of 1 year.As many as 10% ofacutely infectedpatients might

eventually loseserological markers.4/22/2012 32


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Sensitive methods of Diagnosisof HCV infection

Qualitative andquantitative methodsof detection of HCVRNA by

1 Reversetranscriptase RT-PCR,

2 Branched DNA(bDNA)

3 Transcriptionmediated

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CDC guidelines for testing HCVinfection.

Testing for antibodies

Measuring Analineaminotransferase

concentrationTesting for HCV RNA by

PCR at 4 -6 weeks afterexposure and again forantibodies against HCV

and analineaminotransferaseconcentration at 4- 6months

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Prevention and Control

There is no vaccine for HCV infection

Control measures focus on

prevention activities that reduce risksfor contracting HCV

Major guidelines are

1 Screening and testingblood,plasma,organ, tissue,and

semen donors.4/22/2012 35


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Counseling and Educative

measures

Counseling ofpersons with highdrug or sexual

practicesImplementation ofinfection controlpractices in health

care and othersettings.

Professional and

Public education4/22/2012 36


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Treatment in HCV

Optimum timing of treatment is critical toavoid unnecessary treatment of those whowill clear the infection spontaneously

The evidence suggests that it is prudent towait for at least 12 weeks before initiatingantiviral treatment in patients with acuteHepatitis C, especially when they presentwith symptomatic hepatitis CPhysicians select the regimes dependingon the clinical experience and to suit thecircumstances.

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Treatment Regimen

With advent of newer pegylated

Interferons and use has improvedefficacy in patients with chronic HCVinfection, clinicians now use

pegylated interferon as first linetherpay,high sustained Virologicalresponse rates have been reported.

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N I t i HCV


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New Improvements in HCVTreatment

HCV treatment improved again in

2001 with FDA approval of pegylated

interferon. Attaching the polyethyleneglycol (PEG) molecule to interferon (aprocess called pegylation) keeps the

drug in the bloodstream longer andmakes it more effective against HCV.

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P l t d I t f


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Pegylated Interferonsreplaces

Replacing standard interferon withpegylated interferon has significantlyimproved response to HCV treatment and

requires a dosing regimen of only oneinjection per week . Currently, therapy withpegylated interferon plus ribavirin is the

standard treatment of HCV in HIV-positivepeople and the only FDA-approvedtreatment for coinfection.

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P i i i HCV


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Preventive strategies in HCVInfection

As there is no effective vaccine ,preventiveaspects should carry priority on

Universal screening of Blood and Bloodproducts

Sterilization of medical and dentalequipment.

Mandatory used of disposable needles,avoidance of unnecessary injections or

surgical procedures.Health workers, and public should beeducated about the risk of infection from

unsafe practices.Dr.T.V.Rao MD

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Created by Dr.T.V.Rao MDfor Medical and Health

Workers in the Developing

World

[email protected]

hepatitis c infection an update

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